Recent experimental studies show that joint nuclear-cytoplasmic surveys allow unique inferences about many important evolutionary processes in human populations. This special utility derives from the fact that genes in the nucleus are inherited through both parents, while an individual's cytoplasmically-housed genes, such as those in their mitochondria, are usually inherited solely through the mother. As a result of this asymmetrical transmission, the joint nuclear-cytoplasmic makeup of a population provides a new way for detecting a zone of genetic or racial admixture between two populations, as well as qualitatively new information about such key questions as the patterns of mating, selection, and migration within such zones. The proposed research will develop the necessary theoretical and statistical frameworks for unlocking the novel information encoded by nuclear-cytoplasmic data within these and other important human genetic contexts. The practical utility of these new approaches will be demonstrated by applications to a variety of recent data sets from both human and model plant and animal systems. New frameworks also will be developed to delimit the evolutionary consequences of the recently discovered, joint nuclear- mitochondrial etiology of many human genetic diseases, with particular attention given to the fascinating findings that nuclear genes can induce mitochondrial mutations triggering disease onset. A parallel line of research will provide a conceptual framework for understanding the fundamental questions of how and why cytoplasmic inheritance patterns evolve through time. This seminal theoretical study is motivated by the growing number of cases in which mitochondrial and other cytoplasmically-based genes are inherited through the father or both parents, instead of solely through the mother. Moreover, the pattern of inheritance may evolve through time under the control of nuclear or cytoplasmic genes within the parents or progeny. These exciting new discoveries will form the basis of an extensive series of models designed to delimit the conditions favoring evolution among the three cytoplasmic inheritance patterns, and answer the intriguing question of why strict maternal transmission now seems to predominate in humans and other higher organisms.